WHO guidelines for treatment of diarrhoea in HIV patients may need revising in some settings, says study

The World Health Organisation’s (WHO) 1991 guidelines for the management of persistent diarrhoea in HIV-positive patients in resource limited countries may need revising in some settings, according to a study conducted in Peru and published in the on-line version of the January 1^st edition of the Journal of Infectious Diseases.

Current WHO guidelines recommend co-trimoxazole prophylaxis for persistent diarrhoea in HIV-positive patients. However, US and Peruvian investigators found that only 24% of the pathogens causing diarrhoea were susceptible to co-trimoxazole, but that ciprofloxacin, doxycycline and erythromycin were all widely effective.

It is estimated that 95% of HIV-positive individuals in resource-limited setting have persistent diarrhoea. This can cause poor absorption, significant weight loss and is associated with a higher incidence of non-intestinal opportunistic infections and death.

The causes of persistent diarrhoea amongst HIV-positive patients in Latin America has received little attention. Accordingly, investigators from the US and Peru determined to establish the correlation between persistent diarrhoea and microbial causes, the causes of persistent diarrhoea, and the treatment strategies for persistent diarrhoea used by doctors.

Study design

Investigators designed a case-controlled study and between 1998 and 2000 recruited 147 HIV-positive individuals with persistent diarrhoea and 147 HIV-positive patients with no diarrhoea from three major HIV clinics in Peru.

Adult men and non-pregnant women were eligible for inclusion in the study. Persistent diarrhoea was defined as three liquid bowel movements lasting for a week or longer.

In an interview both cases and controls provided investigators with demographic details, HIV risk group, the duration of HIV infection, CD4 cell count, the use of medication to treat diarrhoea, HIV or any other infection, weight loss, medical history, and living conditions. Stool samples were provided by all individuals.

Results

Individuals in both arms of the study had a comparable median age (32 years cases, versus 31 years controls), and approximately two thirds of both cases and controls were men.

Individuals with persistent diarrhoea were significantly less likely to have completed high school education (p = 0.01), have running water at home (p = 0.04) and were more likely to share sanitary facilities with another household (p = 0.002).

In the two months before entry to the study, 66% of all patients were taking co-trimoxazole, including 79% of patients with persistent diarrhoea and 68% without diarrhoea. Anti-tuberculosis treatment was being taken by 9% of cases and 37% control patients, and antiretroviral or antimycotic treatment was 8% of cases and 9% of controls.

Unsurprisingly, Giardia and/or Cryptosporidium in stools was strongly associated with the presence of persistent diarrhoea (odds ratio 5.7). Aeromonas species, Camplyobacterm and rotavirus were also significantly associated with persistent diarrhoea.

Pathogen susceptibility to antibiotics

Antimicrobial susceptibility testing was performed by the investigators who established that only 24% of the pathogens isolated from patients with or without diarrhoea were susceptible to co-trimoxazole, including only 16% of Shigella species, 7% of Aeromonas species, 50% of Camplobacter species and 33% of Salmonella species. By contrast all but one species of Shigella, Salmonella and Aeromonas were susceptible to ciprofloxacin and all Campylobacter species were susceptible to doxycline, with erythromycin also effective against 75%.

Risk factors

The investigators were surprised to note a trend for a higher prevalence of persistent diarrhoea amongst heterosexuals than amongst men who reported sex with other men as their HIV risk factor (p = 0.08).

Individuals with diarrhoea had significantly lower mean CD4 cell counts (p Giardia and that keeping ducks was predictive of Shigella.

“Enteric pathogens were identified in 21% of HIV-infected control subjects without diarrhoea and 55% of HIV-infected case subjects with diarrhoea”, write the investigators.

They note that current WHO guidelines recommend initial therapy with co-trimoxazole for the management of chronic diarrhoea in HIV-positive individuals. However, the investigators note that this strategy is “not optimal for Peru.”

“Most bacterial pathogens we found remained susceptible to ciprofloxacin, which is…widely available in Peru. The inclusion of metronidazole as a first-line drug for patients unable to return to the clinic frequently or as a treatment for those who do not respond to fluoroquinolones should also be considered, in view of the relatively high frequency of giardiasis”, add the investigators, who conclude, “further studies will be necessary to evaluate the effect of revised treatment algorithms.”